US20140128990A1 - Bone putty - Google Patents

Bone putty Download PDF

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Publication number
US20140128990A1
US20140128990A1 US14/110,087 US201214110087A US2014128990A1 US 20140128990 A1 US20140128990 A1 US 20140128990A1 US 201214110087 A US201214110087 A US 201214110087A US 2014128990 A1 US2014128990 A1 US 2014128990A1
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poly
implant material
material according
granules
lactide
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David Franklin Farrar
Nicola Jayne MacAuley
John Rose
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Smith and Nephew PLC
Smith and Nephew Inc
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Smith and Nephew Inc
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Priority claimed from GBGB1105642.1A external-priority patent/GB201105642D0/en
Priority claimed from GBGB1105621.5A external-priority patent/GB201105621D0/en
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Assigned to SMITH & NEPHEW, INC. reassignment SMITH & NEPHEW, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROSE, JOHN, SMITH & NEPHEW PLC
Assigned to SMITH & NEPHEW, INC. reassignment SMITH & NEPHEW, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SMITH & NEPHEW PLC
Assigned to SMITH & NEPHEW PLC reassignment SMITH & NEPHEW PLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SMITH & NEPHEW UK LIMITED
Assigned to SMITH & NEPHEW PLC reassignment SMITH & NEPHEW PLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SMITH & NEPHEW UK LIMITED
Assigned to SMITH & NEPHEW UK LIMITED reassignment SMITH & NEPHEW UK LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MACAULEY, NICOLA JAYNE
Assigned to SMITH & NEPHEW UK LIMITED reassignment SMITH & NEPHEW UK LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FARRAR, DAVID FRANKLIN
Assigned to SMITH & NEPHEW, INC. reassignment SMITH & NEPHEW, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROSE, JOHN
Publication of US20140128990A1 publication Critical patent/US20140128990A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0036—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0084—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing fillers of phosphorus-containing inorganic compounds, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0089—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention relates to bone void fillers.
  • the present invention relates to a macroporous material for filling bone voids.
  • the present invention concerns macroporous materials for bone repair and bone void filling.
  • the material should be mouldable/formable so that it can fill and conform to irregular shaped and sized bone defects. However, once implanted it ideally should set hard so that the implant material maintains its shape and, under some circumstances, be able to bear loads.
  • the material should not break up and needs to be tough. Furthermore, the material should allow rapid bone in-growth and, ultimately, be degradable and fully replaced by bone.
  • the material may incorporate a drug or bioactive molecule which is released to stimulate bone healing and repair.
  • Poly(methyl methacrylate) bone cements are widely used to fixate joint replacements but these materials are non-porous and non-degradable so they are not replaced by bone.
  • heat is generated and the temperature of the material can rise to 90° C. or above. This can damage any drug material or bioactive agent which have been added to the cement, particularly if the bioactive agent consist of proteins such as bone morphogeneic protein (BMP) etc.
  • BMP bone morphogeneic protein
  • Calcium phosphate ceramics such as hydroxyapatite and tricalcium phosphate, are widely used for bone void filling. These fillers are available in a number of forms. For example, the use of dense and porous granules is known. These can be used to fill irregular shaped defects and allow bone growth into and between the granules. However, they cannot maintain a specific shape or form, and tend to migrate if not fully contained. Porous blocks in pre-formed shapes are also known. However, whilst these kinds of fillers maintain their shape, they cannot be used to fill irregular sized/shaped defects.
  • Calcium phosphate cements have also been used as bone fillers. These kinds of fillers have the advantage of being mouldable, and even injectable, and once in place they set hard. However, whilst they may contain micropores, these tend not to allow significant levels of bone ingrowth. Some calcium phosphate cements have macropores but these generally compromise the mechanical strength of the material. In addition, calcium phosphate ceramics (blocks, cements etc) generally tend to form brittle materials.
  • US 2010/0041770 discloses a composite material formed by mixing a polymer phase with a solvent, adding a bioresorbable ceramic phase, and thereafter allowing the solvent to diffuse out of the polymer in the presence of water, to cause solidification of the polymer phase.
  • the composite formed does not have initial porosity for rapid bone in-growth, though pores may form later by degradation of one of the phases.
  • US 2005/0251266 discloses a mouldable composite comprising ceramic granules coated with a biocompatible polymer and a plasticizer such that the polymer is initially deformable and then hardens upon removal of the plasticizer by placing in water.
  • coating the granules is difficult and the specialist processes which need to be employed leads to an increase in cost.
  • the present invention seeks to address at least some of these problems by providing a macroporous material for filling bone voids, which preferably includes one or more of the following characteristics: is mouldable/formable; sets to a hard and tough material; is able to bear loads; allows for rapid bone in-growth; and is biodegradable and substantially replaced by bone without substantially compromising the structural integrity of the site of application.
  • the present invention provides a bone void filler comprising a bioresorbable granulated polymer and a biocompatible water-miscible solvent.
  • an implant material for bone void filling comprising bioresorbable polymer granules and a biocompatible water-miscible solvent, wherein the solvent at least partially dissolves and/or softens the polymer granules to form a mouldable mass that can be used to fill a bone defect, but which hardens when the implant material is exposed to water, and wherein the implant material has macroporosity suitable for bone in-growth.
  • the implant material contains pores of between about 50 and 3000 microns; preferably 100 and 2000 microns; more preferably 120 and 1500 microns, which pores provide a macroporosity level suitable for bone in-growth.
  • the implant material has an open porosity greater than 15%.
  • the implant material has an open porosity of between about 15%-70%; more preferably about 20%-55%; most preferably about 25%-45%.
  • the granules soften and/or partially or fully dissolve causing them to become “sticky” and form a mouldable or flowable mass that can be delivered to the bone defect and which conforms to the shape of the defect.
  • the solvent is removed and the implant material hardens into a mass with interconnected macroporosity.
  • the bioresorbable polymer granules include particles, flakes or powder.
  • the implant material further includes a bioceramic material.
  • the bioceramic material is formed as a mixture with the bioresorbable polymer.
  • the bioceramic material comprises granules, flakes or powder.
  • the powder may be dispersed within the bioresorbable polymer or bioresorbable polymer granules.
  • the bioceramic material is porous.
  • the bioceramic material contains pores of between about 10 and 1000 microns; preferably 15 and 500 microns; more preferably 20 and 300 microns.
  • the bioresorbable polymer granules include a core formed of a different material.
  • the core is formed from a second bioresorbable polymer which is different to the polymer of the bioresorbable polymer granules.
  • the core is formed from a bioceramic material.
  • the bioceramic material is a bioceramic granule or powder.
  • the core includes an inner core and an outer core, wherein the inner core is formed from a bioceramic material and the outer core is formed from a second bioresorbable polymer.
  • the core may also be formed from a bioresorbable polymer having a bioceramic powder dispersed therein. In such embodiments, the powder may be uniformly or non-uniformly dispersed.
  • the implant material includes a bioactive or therapeutic agent.
  • the core includes a bioactive or therapeutic agent.
  • the outer core includes a bioactive or therapeutic agent.
  • the bioactive or therapeutic agent includes at least one of: a growth factor such as any bone morphogenic protein (BMP), platelet derived growth factor (PDGF), growth hormone, transforming growth factor-beta (TGF-beta), insulin-like growth factor; a bisphosphonate such as alendronate, zoledronate; an antibiotic such as gentamicin, vancomycin, tobramicin; an anti-cancer drug such as paclitaxel, mercatopurine; an anti-inflammatory agent such as salicylic acid, indomethacine; an analgesic such as salicylic acid.
  • BMP bone morphogenic protein
  • PDGF platelet derived growth factor
  • TGF-beta transforming growth factor-beta
  • insulin-like growth factor e.g., insulin-like growth factor
  • a bisphosphonate such as alendronate, zoledronate
  • an antibiotic such as gentamicin, vancomycin, tobramicin
  • the bioactive or therapeutic agent may also be incorporated into the implant material by: coating onto the bioceramic granules; incorporating within the bioceramic granules; coating onto the polymer granules; incorporating within the polymer granules; incorporating within the biocompatible solvent; adding at the time of mixing the components or any combination of these methods to give a desired dispersion and release profile.
  • the second bioresorbable polymer is less soluble in the biocompatible solvent than the first bioresorbable polymer.
  • the surface of the bioresorbable polymer granules becomes softened and/or partially dissolves but the outer core layer, preferably containing a bioactive or therapeutic agent, remains largely intact.
  • the bioactive or therapeutic agent will be released from the outer core layer as the first bioresorbable polymer is absorbed.
  • the same or a different bioactive or therapeutic agent can be incorporated into the first bioresorbable polymer.
  • the bioactive or therapeutic agents are the same they have different release rates according to the different release characteristics and/or degradation rates of the first and second bioresorbable polymers.
  • the bioceramic granules include at least one of: calcium phosphate, including hydroxyapatite, any substituted hydroxyapatite (e.g. silicon, carbonate, magnesium, strontium, fluoride), tricalcium phosphate, biphasic calcium phosphate, tetracalcium phosphate, octacalcium phosphate, dicalcium phosphate dihydrate (brushite), dicalcium phosphate (monetite), calcium pyrophosphate, calcium pyrophosphate dihydrate, heptacalcium phosphate, calcium phosphate monohydrate; calcium sulphate; any bioactive glass (e.g. Bioglass) or glass ceramic (e.g. apatite-wollastonite); or any combination of these.
  • the granules may be dense or porous.
  • the first bioresorbable polymer includes at least one of: any polymer from the poly-alpha-hydroxyacid group, including poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(L-lactide-co-DL-lactide), polycaprolactone; any bioresorbable polyanhydride, polyamide, polyorthoester, polydioxanone, polycarbonate, polyaminoacid, poly(amino-ester), poly(amido-carbonate), polyphosphazene, polyether, polyurethane, polycyanoacrylate, or any combination of these.
  • any polymer from the poly-alpha-hydroxyacid group including poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-glycolide), poly(lact
  • the second bioresorbable polymer includes at least one of: a polymer from the poly-alpha-hydroxyacid group, including poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(L-lactide-co-DL-lactide), polycaprolactone; any bioresorbable polyanhydride, polyamide, polyorthoester, polydioxanone, polycarbonate, polyaminoacid, poly(amino-ester), poly(amido-carbonate), polyphosphazene, polyether, polyurethane, polycyanoacrylate; a polysaccharide optionally including alginate, chitosan, carboxymethyl cellulose, hydroxypropylmethyl cellulose, dextran, hyaluronic acid, or any combination of these.
  • the biocompatible, water miscible solvent includes at least one of: N-methyl-pyrollidone, dimethyl sulphoxide, acetone, poly(ethylene glycol), tetrahydrofuran, isopropanol, or caprolactone.
  • the implant material includes a water soluble porogen that is not soluble in the biocompatible solvent.
  • the water soluble porogen includes at least one of: a soluble inorganic salt such as sodium chloride; any soluble organic compound such as sucrose; or a water soluble polymer such as poly(ethylene glycol), poly(vinyl alcohol), polysaccharide such as carboxymethylcellulose.
  • aspects of the present invention are macroporous and fully bioresorbable.
  • aspects of the present invention have the advantage of being injectable and/or mouldable and capable of conforming to irregular shaped bone defects.
  • aspects of the present invention have the advantage of hardening in-situ to form a cohesive mass, thus preventing the possibility of granules migrating.
  • This could be particularly advantageous when the implant is being used to deliver a drug or therapeutic agent, particularly one which stimulates bone formation, such as BMP, as it reduces the possibility of bone forming in unwanted areas—particularly important if the implant is being used in areas such as the spine where there may be nerves etc near to the bone implant.
  • aspects of the invention described here have the advantage of having immediate connected macroporosity suitable for rapid bone in-growth.
  • aspects of the present invention keep at least some of the bioactive/therapeutic molecule within an intact coating layer which is not removed from the granules when the biocompatible solvent is added. This allows for better control and sustained release of the molecule. Also, in embodiments having more than one layer of polymer coating with different release and/or degradation profiles, the overall release of drug can be tailored or the system used to deliver different compounds with different release profiles.
  • aspects of the invention do not require pre-coating of the ceramic granules, and furthermore, the fact that a portion of the granules comprise a bioresorbable polymer allows for the creation of greater porosity as the polymer granules degrade allowing more room for bone in-growth over time.
  • the viscosity of the implant material prior to hardening can be adjusted by the addition of water after the addition and mixing of the solvent. If an injectable/flowable material is desired then no water is added but by adding water prior to implantation a more putty-like/mouldable consistency can be achieved.
  • FIG. 1 is a schematic illustration of a first embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 2 is a schematic illustration of a second embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 3 is a schematic illustration of a third embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 4 is a schematic illustration of a fourth embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 5 is a schematic illustration of a fifth embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 6 is a schematic illustration of a sixth embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 7 is a schematic illustration of a seventh embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 8 is a schematic illustration of an eighth embodiment, according to the present invention, of an implant material for bone void filling
  • FIG. 9 is a schematic illustration of a ninth embodiment, according to the present invention, of an implant material for bone void filling.
  • FIG. 10 is a close-up schematic view of the embodiment of FIG. 9 .
  • an implant material precursor for bone void filling comprising polymer granules 10 and a biocompatible solvent 11 .
  • the solvent 11 softens and tackifies the outer surface of the polymer granules, giving them a ‘sticky’ character. In this state, the granules adhere together to form a cohesive, mouldable implant material.
  • the implant material can then be used to fill bone voids and defects (not shown).
  • the biocompatible solvent is preferably water-miscible. In the presence of water or an aqueous environment, such as being placed in the body, the solvent is removed and the implant material hardens into a mass with interconnected macroporosity. Consequently, the macroporous material allows for tissue ingrowth, particularly bone tissue ingrowth.
  • the polymer granules are formed from biosorbable materials such as poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(L-lactide-co-DL-lactide), polycaprolactone; any bioresorbable polyanhydride, polyamide, polyorthoester, polydioxanone, polycarbonate, polyaminoacid, poly(amino-ester), poly(amido-carbonate), polyphosphazene, polyether, polyurethane, polycyanoacrylate, or any combination of these, and as the polymer degrades and is absorbed by the body new bone forms and advances to replace substantially all of the polymer material.
  • biosorbable materials such as poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-g
  • the biocompatible water miscible solvent may be selected from: N-methyl-pyrollidone, dimethyl sulphoxide, acetone, poly(ethylene glycol), tetrahydrofuran, isopropanol, or caprolactone.
  • a porogen 12 can be incorporated in the implant material leading to the formation of further macropores within the set composition.
  • the porogen will be a soluble inorganic salt such as sodium chloride; a soluble organic compound such as sucrose; or a water soluble polymer such as poly(ethylene glycol), poly(vinyl alcohol), polysaccharide such as carboxymethylcellulose.
  • the implant material may also include a bioceramic material in the form of granules 13 , as illustrated in FIG. 3 .
  • the bioceramic material may be at least one of: calcium phosphate, including hydroxyapatite, a substituted hydroxyapatite (e.g.
  • the solvent softens and tackifies the outer surface of the polymer granules, making them sticky.
  • the granules then adhere to each other and also the bioceramic granules, and as the solvent is removed, the polymer hardens and incorporates the bioceramic granules in the set macroporous structure.
  • the bioceramic granules add strength and rigidity to the implant material, and are osteoconductive to encourage bone in-growth. Further, because only the outer surface of the polymer granules is softened, the polymer does not spread to coat the surface of the bioceramic granules, and therefore much of the outer surface of the bioceramic granules remains exposed. Accordingly, there is substantially no delay to initiation of the osteoconductive effect.
  • the biocompatible solvent fully dissolves the polymer granules in the presence of the bioceramic granules and forms a coating 14 over each surface. This can be achieved in the presence or absence of a porogen. Alternatively, a similar result can be achieved by pre-mixing the solvent and polymer and then adding the bioceramic granules, and optionally a porogen, to this mixture in order to form the implant material ( FIGS. 7 and 8 ).
  • the implant material may also include a bioactive or therapeutic agent.
  • a growth factor such as a bone morphogenic protein (BMP), platelet derived growth factor (PDGF), growth hormone, transforming growth factor-beta (TGF-beta), insulin-like growth factor; a bisphosphonate such as alendronate, zoledronate; an antibiotic such as gentamicin, vancomycin, tobramicin; an anti-cancer drug such as paclitaxel, mercatopurine; an anti-inflammatory agent such as salicylic acid, indomethacine; or an analgesic such as salicylic acid.
  • BMP bone morphogenic protein
  • PDGF platelet derived growth factor
  • TGF-beta transforming growth factor-beta
  • insulin-like growth factor such as alendronate, zoledronate
  • a bisphosphonate such as alendronate, zoledronate
  • an antibiotic such as gentamicin, vancomycin, tobramicin
  • the bioresorbable polymer granules include a core formed of a different material.
  • the core material may be a different bioresorbable polymer, having different properties to the first bioresorbable polymer granules, or may be a bioceramic material. In embodiments which incorporate a bioceramic core, the material will be a bioceramic granule or powder.
  • the core includes an inner core and an outer core, where the inner core is formed from a bioceramic material and the outer core is formed from a second bioresorbable polymer.
  • a polymer granule formed from a first bioresorbable polymer includes a core having an inner core formed from a bioceramic material, and an outer core, formed from a second bioresorbable polymer.
  • the first bioresorbable polymer will be at least partially soluble in the biocompatible solvent so that it provides adhesion between granules. If the first bioresorbable polymer includes a bioactive or therapeutic agent, it may provide an initial release of that agent as the polymer starts to degrade and be absorbed.
  • the second bioresorbable polymer may be: a polymer comprising a poly-alpha-hydroxyacid group, including poly(lactic acid), poly(glycolic acid), poly-L-lactide, poly-DL-lactide, poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(L-lactide-co-DL-lactide), polycaprolactone; any bioresorbable polyanhydride, polyamide, polyorthoester, polydioxanone, polycarbonate, polyaminoacid, poly(amino-ester), poly(amido-carbonate), polyphosphazene, polyether, polyurethane, polycyanoacrylate; a polysaccharide comprising alginate, chitosan, carboxymethyl cellulose, hydroxypropylmethyl cellulose, dextran, hyaluronic acid, or any combination of these.
  • the second bioresorbable polymer is generally less soluble in the
  • the sample was stored overnight in deionized water at 37° C. After 24 hours the cylindrical samples were all cut to a height of 1.5 cm and tested in compression using an Instron 5569 Universal Testing Machine at a rate of 5 mm/min.
  • Example 1 was repeated but this time 1 ml of NMP was added. In this case the polymer granules fully dissolved and a solid plug was formed with less visible porosity.
  • the sample was stored in deionized water at 37° C. and tested in compression as described in Example 1. Compression testing gave a yield stress of 4 MPa. There was no peak in the stress-strain curve indicating a tough material.
  • 0.5 ml of TCP was mixed with 0.5 ml sucrose (granulated—supplied by Sigma-Aldrich, Product Code 84097) and 0.5 ml PDLGA 85:15.
  • 0.5 ml NMP was added to the mixture and stirred and kneaded with a spatula to form a putty. Again the mixture was packed into the mould then pushed out into water. After about 5 minutes the sample was removed and examined and seen to have hardened. Pores were visible between the granules and also from the dissolution of the sucrose.
  • the sample was stored in deionized water at 37° C. and tested in compression as described in Example 1. The sample gradually collapsed under compression and no yield point or peak stress was visible on the stress-strain curve.
  • Example 3 0.5 ml TCP was mixed with 0.5 ml sucrose and 0.25 ml PDLGA 85:15. 1 ml of NMP was added. As for Example 3, a flowable system was formed. 0.5 ml water was added and this caused the mixture to form a putty-like consistency. Again it was packed into the mould and pushed out into water. After about 5 minutes the sample was examined and seen to have hardened. Pores were visible between the granules and also from the dissolution of the sucrose. The sample was stored in deionized water at 37° C. and tested in compression as described in Example 1. The sample gradually collapsed under compression and no yield point or peak stress was visible on the stress-strain curve.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was prepared for Micro-CT analysis by mounting the bone void filler specimen directly onto a brass pin sample holder using an adhesive tab on the base of the bone void filler.
  • Micro-CT images were acquired on a Skyscan 1173 Micro-CT using a micro focused X-ray source with a voltage of 85 kV and a current of 68 ⁇ A.
  • X-ray shadow images were acquired with a 0.4 deg step size over a 180 deg acquisition angle, with 4 averages and 6 ⁇ m resolution.
  • the X-ray shadow images were reconstructed into a stack of 2D cross-sections using a reconstruction program (N-Recon) supplied by Skyscan.
  • the Micro-CT images were reconstructed using a smoothing factor of 2, a ring artefact correction of 12 and a beam hardness correction factor between 50%-65%.
  • the sample was then tested in compression using an Instron 5569 Universal testing Machine at a rate of 2.5 mm/min.
  • the sample had a compressive modulus of 2.33 MPa and a failure stress of 0.13 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 77.0 MPa and a failure stress of 3.78 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 1.92 MPa and a failure stress of 0.14 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus 3.21 and a failure stress of 0.18 MPa.
  • a 33.3% w/w solution of PLGA 85:15 in NMP was prepared by mixing 3 g PDLGA with 6 g NMP and allowing to stand overnight at room temperature until the polymer was fully dissolved.
  • the sample was stored in deionized water for 3 days and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 3.96 MPa and a failure stress of 0.24 MPa.
  • the sample was stored in deionized water for 3 days and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 13.3 MPa and a failure stress of 0.37 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 31.5 MPa and a failure stress of 1.52 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 6.07 MPa and a failure stress of 2.13 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 26.5 MPa and a failure stress of 3.65 MPa.
  • the sample was stored in deionized water for 24 hours and then removed and air dried.
  • the sample was analysed by micro-CT as described in Example 12.
  • the results from the micro-CT scanning were as follows:
  • the sample was then tested in compression as described in Example 12.
  • the sample had a compressive modulus of 0.97 MPa and a failure stress of 0.16 MPa.
  • Table 1 summarises the compositions and results from Examples 1-11 Compression Test Load at Peak Example PDLGA Porogen Ceramic PDLGA Solvent Porogen Yield Load No. Ceramic Type Type Type Solvent Vol. (ml) Vol. (ml) Vol. (ml) Vol.
  • the results in tables 1 and 3 show that materials able to withstand stresses up to 5 MPa or higher are achievable, while still maintaining a high level of porosity.
  • the compressive strength of cancellous bone is typically in the range 2-12 MPa so it can be seen that it is possible to make bone void filling materials with strengths in this range (Examples 1, 2, 13, 19 and 20).
  • the Young's modulus of cancellous bone is typically in the range 4-350 MPa and it can also be seen that it is possible to make materials with compressive moduli in this range (Examples 13, 16, 17, 18, 19, 20).

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GBGB1105642.1A GB201105642D0 (en) 2011-04-04 2011-04-04 Bone repair putty
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GB105621.5 2011-04-04
GBGB1105621.5A GB201105621D0 (en) 2011-04-04 2011-04-04 Bone repair putty
PCT/US2012/032066 WO2013165333A1 (fr) 2011-04-04 2012-04-04 Mastic osseux

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US20190151418A1 (en) * 2016-04-08 2019-05-23 Toyobo Co., Ltd. Combination of calcium-phosphate-containing porous composite and pth

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US20170056559A1 (en) 2014-03-14 2017-03-02 Ecole Polytechnique Federale De Lausanne (Epfl) Active Agent-Particle Combination Supporting Bone Regeneration
CN108939150A (zh) * 2018-09-05 2018-12-07 华东理工大学 基于POFC/β-TCP和雷尼酸锶的骨质疏松缺损修复用支架
CN109666274A (zh) * 2018-12-27 2019-04-23 广州云瑞信息科技有限公司 一种高强度可吸收骨折内固定材料及其制备方法
US20220323641A1 (en) * 2019-08-20 2022-10-13 Theradaptive, Inc. Materials for delivery of tetherable proteins in bone implants
EP3954402A4 (fr) * 2019-08-31 2023-01-11 Shenzhen Corliber Scientific Co., Ltd. Matériau composite d'os artificiel en plastique et procédé de préparation associé
CN110801537B (zh) * 2019-08-31 2021-04-23 深圳市立心科学有限公司 可塑形的人工骨复合材料及其制备方法
WO2022140954A1 (fr) * 2020-12-28 2022-07-07 Brilliance Biomedicine Co., Ltd. Composite osseux biodégradable et injectable et ses utilisations
CN113521377B (zh) * 2021-09-13 2022-04-05 诺一迈尔(山东)医学科技有限公司 可生物降解的组织粘合剂及其制备方法
CN116253986B (zh) * 2023-03-31 2024-05-03 浙江理工大学 一种水性高效生物质抗菌阻燃聚氨酯的制备方法
CN117427224B (zh) * 2023-11-15 2025-07-22 西安理工大学 温度响应脉冲式长效降解磷酸钙骨水泥及制备方法

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